Increased Activity and Expression of Gelatinases in Ischemic Colitis

Ischemic colitis results from insufficient blood supply but its pathogenesis is poorly understood. The aim of this study was to determine whether the activity and expression of gelatinases (MMP-9 and MMP-2) are increased in the colonic mucosa of patients with ischemic colitis. MMP-9 and MMP-2 activity and expression were assessed in colonic mucosal specimens from 8 patients with acute ischemic colitis and in 12 controls with a normal colonoscopy. The activity and expression of MMP-9 and MMP-2 were quantified in tissue samples by zymography and western blot, respectively. Colonoscopy was repeated 12 weeks after discharge in two patients and MMP activity was assessed in the slight residual mucosal changes of ischemic colitis. In patients with ischemic colitis, a significant increase in total MMP-9 and MMP-2 activity and expression was found in ulcerated areas compared with noninvolved sites of mucosa. Following resolution of ischemic ulcers the proteolytic activity returned to baseline levels. In addition, the colonic mucosa of controls showed MMP-2 activity, whereas the MMP-9 activity was negligible or not detected. We conclude that ischemic colitis induces increased activity and expression of MMP-9 and MMP-2 in the involved colonic mucosa. These changes may contribute to tissue degradation and remodeling of the colonic mucosa in ischemic colitis.